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Pronunciation
(hye droe klor oh THYE a zide)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of mild-to-moderate hypertension; treatment of edema in heart failure and nephrotic syndrome
Use: Unlabeled/Investigational
Treatment of lithium-induced diabetes insipidus
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies. Thiazide diuretics cross the placenta and are found in cord blood. Maternal use may cause may cause fetal or neonatal jaundice, thrombocytopenia, or other adverse events observed in adults. Use of thiazide diuretics during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Thiazide diuretics are found in breast milk. Following a single oral maternal dose of hydrochlorothiazide 50 mg, the mean breast milk concentration was 80 ng/mL (samples collected over 24 hours) and hydrochlorothiazide was not detected in the blood of the breast feeding infant (limit of detection 20 ng/mL). Peak plasma concentrations reported in adults following hydrochlorothiazide 12.5-100 mg are 70-490 ng/mL.
Contraindications
Hypersensitivity to hydrochlorothiazide or any component of the formulation, thiazides, or sulfonamide-derived drugs; anuria; renal decompensation; pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, and hyponatremia can occur.
• Ocular effects: May cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Risk factors may include a history of sulfonamide or penicillin allergy.
• Photosensitivity: Photosensitization may occur.
• Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns:
• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.
• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated.
• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.
• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations.
• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy.
• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use.
• Renal impairment: Avoid in severe renal disease (ineffective).
• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.
Adverse Reactions
Frequency not defined; adverse events reported were observed at doses ≥25 mg:
Cardiovascular: Hypotension, orthostatic hypotension
Central nervous system: Dizziness, fever, headache, vertigo
Dermatologic: Alopecia, erythema multiforme, exfoliative dermatitis, photosensitivity, purpura, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Hyperglycemia, hypokalemia, hyperuricemia
Gastrointestinal: Anorexia, constipation, cramping, diarrhea, epigastric distress, gastric irritation, nausea, pancreatitis, sialadenitis, vomiting
Genitourinary: Glycosuria, impotence
Hematologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia
Hepatic: Jaundice
Neuromuscular & skeletal: Muscle spasm, paresthesia, restlessness, weakness
Ocular: Blurred vision (transient), xanthopsia
Renal: Interstitial nephritis, renal dysfunction, renal failure
Respiratory: Respiratory distress, pneumonitis, pulmonary edema
Miscellaneous: Anaphylactic reactions, necrotizing angiitis
<1% (Limited to important or life-threatening): Allergic myocarditis, eosinophilic pneumonitis, hepatic function impairment, hypercalcemia
Drug Interactions
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
CarBAMazepine: Thiazide Diuretics may enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Licorice: May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
OXcarbazepine: Thiazide Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification
Topiramate: Thiazide Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Risk D: Consider therapy modification
Toremifene: Thiazide Diuretics may enhance the hypercalcemic effect of Toremifene. Risk C: Monitor therapy
Vitamin D Analogs: Thiazide Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Hydrochlorothiazide peak serum levels may be decreased if taken with food. This product may deplete potassium, sodium, and magnesium.
Herb/Nutraceutical: Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of hydrochlorothiazide. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of hydrochlorothiazide.
Mechanism of Action
Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions
Pharmacodynamics/Kinetics
Onset of action: Diuresis: ~2 hours
Peak effect: 4-6 hours
Duration: 6-12 hours
Absorption: ~50% to 80%
Distribution: 3.6-7.8 L/kg
Protein binding: 68%
Metabolism: Not metabolized
Bioavailability: 50% to 80%
Half-life elimination: 5.6-14.8 hours
Time to peak: 1-2.5 hours
Excretion: Urine (as unchanged drug)
Dosage
Oral (effect of drug may be decreased when used every day):
Children (in pediatric patients, chlorothiazide may be preferred over hydrochlorothiazide as there are more dosage formulations [eg, suspension] available): Edema, hypertension:
<6 months: 1-3 mg/kg/day in 2 divided doses
>6 months to 2 years: 1-3 mg/kg/day in 2 divided doses; maximum: 37.5 mg/day
>2-17 years: Initial: 1 mg/kg/day; maximum: 3 mg/kg/day (50 mg/day)
Adults:
Edema: 25-100 mg/day in 1-2 doses; maximum: 200 mg/day
Hypertension: 12.5-50 mg/day; minimal increase in response and more electrolyte disturbances are seen with doses >50 mg/day
Elderly: 12.5-25 mg once daily
Dosing adjustment/comments in renal impairment: Clcr <10 mL/minute: Avoid use. Usually ineffective with GFR <30 mL/minute. Effective at lower GFR in combination with a loop diuretic.
Note: ACC/AHA 2009 Heart Failure guidelines suggest that thiazides lose their efficacy when Clcr <40 mL/minute.
Administration: Oral
May be administered with food or milk. Take early in day to avoid nocturia. Take the last dose of multiple doses no later than 6 PM unless instructed otherwise.
Monitoring Parameters
Assess weight, I & O reports daily to determine fluid loss; blood pressure, serum electrolytes, BUN, creatinine
Test Interactions
May interfere with parathyroid function tests. Tyramine and phentolamine tests, histamine tests for pheochromocytoma.
Dietary Considerations
May be taken with food or milk.
Patient Education
Follow prescriber's instructions for diet and lifestyle changes. Take with meals early in the day to avoid nocturia. Your physician may prescribe a potassium supplement or recommend that you eat foods high in potassium. Do not change your diet on your own while taking this medication, especially if you are taking potassium supplements or medications to reduce potassium loss. May cause dizziness, postural hypotension, or photosensitivity. Report palpitations, muscle cramping, or skin rash.
Geriatric Considerations
Hydrochlorothiazide is not effective in patients with a Clcr <30 mL/minute, therefore, it may not be a useful agent in many elderly patients.
Additional Information
If given the morning of surgery, hydrochlorothiazide may render the patient volume depleted and blood pressure may be labile during general anesthesia. Effect of drug may be decreased when used every day.
Anesthesia and Critical Care Concerns/Other Considerations
If given the morning of surgery, hydrochlorothiazide may render the patient volume depleted and blood pressure may be labile during general anesthesia.
Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker.
Cardiovascular Considerations
Hypertension: Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker. The initial concern about thiazide diuretic-induced hypokalemia, glucose intolerance, and lipid profiles does not appear to be of substantial clinical consequence in the treatment of hypertension. The benefits of this class of agents in the treatment of hypertension is established and compares well with other first-line therapeutic agents. The ALLHAT study (ALLHAT Collaborative Group, 2002) compared CV outcomes of lisinopril, amlodipine, or chlorthalidone in hypertensive patients having at least one other risk factor for coronary heart disease. Investigators found no difference between the groups on the primary outcome of fatal coronary disease or nonfatal MI. The JNC 7 recommends diuretics for the treatment of hypertension with concurrent heart failure where diuresis is also required (loop diuretics may more frequently be required), high coronary disease risk (as in the ALLHAT trial), diabetes (beneficial in reducing CVD and stroke incidence), and recurrent stroke prevention (in combination with an ACE inhibitor). Thiazides are useful in slowing demineralization in osteoporosis, but need to be used cautiously in gout and in patients with significant history of hyponatremia.
Diuretics are standard therapy for the management of edema in patients with heart failure. However, it is important to ensure that edema is not secondary to pericardial effusion. Marked reduction in intravascular volume with consequent decreased cardiac filling pressures may precipitate significant hypotension in these circumstances.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic hypotension and hypotension.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Used to treat lithium-induced diabetes insipidus; monitor for hypokalemia; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy (sulfonamides). Assess electrolytes, BUN, and creatinine regularly during therapy. Monitor for hypotension, hypokalemia, and confusion regularly. Caution patients with diabetes to monitor glucose levels closely; may alter glucose control.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 12.5 mg
Microzide®: 12.5 mg
Tablet, oral: 12.5 mg, 25 mg, 50 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Hydrochlorothiazide)
12.5 mg (30): $14.99
Capsules (Microzide)
12.5 mg (30): $36.71
Tablets (Hydrochlorothiazide)
50 mg (100): $15.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Aronoff GR, Berns JS, Brier ME, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults, 4th ed. Philadelphia, PA: American College of Physicians; 1999.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-90.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
Miller ME, Cohn RD, and Burghart PH, "Hydrochlorothiazide Disposition in a Mother and Her Breast-Fed Infant," J Pediatr, 1982, 101(5):789-91.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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